Fox-Fordyce Disease 

Updated: Aug 14, 2017
Author: Christopher R Gorman, MD; Chief Editor: William D James, MD 

Overview

Background

Fox-Fordyce disease is an infrequently occurring chronic pruritic papular eruption that localizes to areas where apocrine glands are found. The etiology of Fox-Fordyce disease currently is unknown. The eponym is based on the 1902 report by G. Fox and J. Fordyce.[1]

Pathophysiology

Fox-Fordyce disease is a disease of the skin alone. In 1956, Shelley and Levy proposed apocrine miliaria as the cause.[2] The observed pathophysiology is a keratin plug in the hair follicle infundibulum obstructing the apocrine acrosyringium and producing an apocrine anhidrosis. Histologically, a rupture of the apocrine excretory duct occurs, and spongiotic inflammation results. Extravasation of sweat and inflammation is postulated to cause the intense itching. Ranalletta et al found that the acrosyringium of the eccrine glands was similarly involved.[3]

In 2003, Kamada et al published a histopathologic analysis from which they concluded that the 2 types of this disease are (1) an apocrine (follicular) type and (2) an apocrine (nonfollicular) type.[4]

Epidemiology

Frequency

Fox-Fordyce disease is an infrequent condition. Geographic influence is not evident. Many case reports of Fox-Fordyce disease mention heat, humidity, and stress as exacerbating factors. Reports of Fox-Fordyce disease from the United States are the most common; however, a geographic limitation is not evident.

Race

No racial predilection is evident for Fox-Fordyce disease.

Sex

A distinct predilection for women exists for Fox-Fordyce disease; the female-to-male ratio is 9:1.

Age

Fox-Fordyce disease is most common in women aged 13-35 years; it is rare before or after this age.

Prognosis

Management with topical retinoids and antibiotics has brought some hope to patients with Fox-Fordyce disease for decades. Long-term follow-up studies are not available; therapy may need to be prolonged for a very long time. Acceptable therapy should be safe and relatively inexpensive.

Fox-Fordyce disease has no risk of loss of life or limb. Patients often experience severe pruritus. Therefore, the patient's quality of life may be adversely affected.

 

Presentation

History

Fox-Fordyce disease frequently appears under conditions of heat, humidity, and friction, often appearing suddenly. Many patients present after decades of symptoms.

Few patients are asymptomatic. Most patients relate pruritus that disturbs sleep.

Changing antiperspirants has not been reported to help. Some patients report diminution of sweating after the onset of symptoms.

Physical Examination

The apocrine glands are the site of Fox-Fordyce disease. Lesions are most often found in the axillae, where they tend to be bilateral. Lesions may also affect the periareolar, inframammary, and pubic areas.

The primary lesion is a flesh-colored to reddish, smooth, dome-shaped, discrete, and follicular or perifollicular papule. Affected areas usually have many papules. The papules usually appear to affect every follicle in a given area. Excoriations and lichenification may be seen as a consequence of scratching.

Sweating is often absent in the affected area.

Causes

The definite increased prevalence of Fox-Fordyce disease in women has led to an unproved theory of hormonal influences. Reports of cases of Fox-Fordyce disease in prepubertal girls are evidence against the hormonal theory. The exact pathophysiology is still unknown.

A number of factors, including (1) emotional and/or hormonal influences and (2) alterations in sweat components, have been implicated in Fox-Fordyce disease.

Fox-Fordyce disease has been reported to occur after laser hair removal.[5, 6, 7, 8]

Complications

Manage Fox-Fordyce disease complications (eg, local superinfection) in the standard ways.

 

DDx

 

Workup

Laboratory Studies

Histopathologic diagnosis of Fox-Fordyce disease may be very difficult with conventional sectioning. Stashower et al proposed transverse histologic sectioning as the most effective way to demonstrate diagnostic features.[9]

Diagnosis of Fox-Fordyce disease is usually made on clinical/historical grounds. Laboratory or even histopathologic tests are seldom necessary for clinicians familiar with this condition.

Procedures

In 2002, Chae et al described axillary Fox-Fordyce disease treated with liposuction-assisted curettage.

Histologic Findings

The proposed apocrine origin of Fox-Fordyce disease was based on the finding of a keratin plug in the follicular infundibulum that occluded the apocrine acrosyringium. Reports also include a rupture of the apocrine duct and a resulting spongiotic inflammation. Plasma cells may be noted, and the deeper apocrine duct may be dilated with sialomucin. The dermis may show fibrosis and chronic inflammation. These latter findings depend on the condition's chronicity.

Transverse sectioning may allow for a more accurate diagnosis of Fox-Fordyce disease. Bormate et al contend that perifollicular xanthomatosis (foam cells) is a specific, relatively consistent, and distinct histologic feature in 7 cases.[10]  Perifollicular xanthomatosis may result in a histologic misdiagnosis of planar xanthoma due to sectioning error (author). Apocrine acini dilation may be another helpful nonspecific histologic finding.[11]

 

Treatment

Medical Care

Many Fox-Fordyce disease patients improve when placed on an oral contraceptive pill. Based on the observations of follicular occlusion, Shelley proposed topical tretinoin cream as therapy in 1972.[2] Reports of success with topical retinoids followed, along with reports of success with topical steroids, topical calcineurin inhibitors, antibiotics, topical clindamycin,[12, 13] clindamycin in alcoholic propylene glycol solution, hormonal therapy in women, ultraviolet light, dermabrasion, and surgical excision. Usually, these therapies were not curative and were often complicated by intolerable irritation. In 1994, Effendy et al reported the short-term success of isotretinoin when given for 4 months in a daily oral dose of 15-30 mg; the condition returned 3 months after cessation of therapy.

Surgical Care

Surgical excision of affected areas in the axilla has been performed in the past, but it is seldom recommended. Chae et al reported treatment of Fox-Fordyce disease with liposuction-assisted curettage.[14]  Pulsed dye laser has been reported as a possibly effective treatment.[15]

Consultations

Consultation with a dermatologist is usually recommended in Fox-Fordyce disease.

Activity

Activity that leads to sweating is counterproductive. Swimming is the preferred form of exercise for Fox-Fordyce disease patients.

Prevention

Environmental modification and hormonal therapy have not always proven to affect the course of Fox-Fordyce disease.

Long-Term Monitoring

Advise patients of the chronicity and the possible need for long-term therapy because Fox-Fordyce disease is often controlled but not cured.

 

Medication

Medication Summary

Medical therapy for Fox-Fordyce disease has been complicated by the irritant potential of the topical medications. Topical steroids have not been useful. Topical retinoids have been irritating, which has limited their long-term use. In 1979, Giacobeti reported success with topical 0.1% tretinoin cream. In 1990, Casani reported treatment with topical 0.5% tretinoin cream. In 1995, Miller et al reported treatment of Fox-Fordyce disease with topical clindamycin solution.[12]

Hormonal therapy for Fox-Fordyce disease with high-estrogen oral contraceptives, estrogen creams, and testosterone creams has been reported.

In 2006, Pock et al reported effective therapy, with no adverse effects, using pimecrolimus in 3 young female patients.[16] The response was deemed "very impressive." Based on this report, the drug of choice could be this class of drug, which includes tacrolimus. Tacrolimus was found to safe and effective in treating one of two patients.[17]

Retinoids

Class Summary

Based on follicular infundibular occlusion, the retinoids (first tretinoin, later isotretinoin) have been used with reported short-term success. Consider therapy with alternative retinoids as they become available. Based on the success of tretinoin, oral retinoids have also been used with reported success.

Tretinoin topical (Avita, Retin-A)

Since 1972, therapy with topical retinoids has the most support in the literature. Several reports exist on the efficacy of topical tretinoin. Severe irritation may occur when used in the axillae. The 0.025% cream, or even a dilution to a milder form or short contact therapy, would be prudent to begin therapy.

Increasing both the time and the amount gradually as tolerated is a safe way to avoid irritation.

Isotretinoin (Accutane)

By analogy, because isotretinoin worked topically, it was predicted that oral retinoids would be effective. Low doses of isotretinoin have been efficacious. Although symptoms were relieved at relatively low doses, the condition returned in a few months after cessation of therapy.

A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

Antibiotics

Class Summary

Topical clindamycin in propylene glycol was first reported to help patients with Fox-Fordyce disease in 1992. Confirmation of this study was reported in 1995. Topical erythromycin should also be helpful.

Clindamycin topical (Cleocin-T)

Clindamycin topical is a lincosamide for the treatment of serious skin and soft tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). It inhibits bacterial growth, possibly by blocking the dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Erythromycin topical (AkneMycin, Ery)

Erythromycin topical inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is used in the treatment of staphylococcal and streptococcal infections.

Immunosuppressive Agents, Topical

Pimecrolimus (Elidel)

Because of the rapidity of response, effectiveness of therapy, and lack of adverse effects, this could be current drug of choice. It is in immunomodulating macrolactam (neuraminidase inhibitors) class of drugs and has significant anti-inflammatory activity and a highly favorable adverse effect profile in at least the short range. It is especially safe to use in the axilla, periareolar, and groin areas.

Tacrolimus ointment (Protopic)

Because of the rapidity of response, effectiveness of therapy, and lack of adverse effects, this could be current drug of choice. It is in immunomodulating macrolactam (neuraminidase inhibitors) class of drugs and has significant anti-inflammatory activity and a highly favorable adverse effect profile in at least the short range. It is especially safe to use in the axilla, periareolar, and groin areas.